JOSE TADEU STEFANO
Projetos de Pesquisa
Unidades Organizacionais
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina
28 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 28
- Ability of a Combined FIB4/miRNA181a Score to Predict Significant Liver Fibrosis in NAFLD Patients(2021) LIMA, Rodrigo Vieira Costa; STEFANO, Jose Tadeu; MALTA, Fernanda de Mello; PINHO, Joao Renato Rebello; CARRILHO, Flair Jose; ARRESE, Marco; OLIVEIRA, Claudia P.Liver biopsy is the gold standard for assessing fibrosis, but there is a need to seek non-invasive biomarkers for this purpose. The aim of this study was to evaluate the correlation between the serum levels of the microRNAs miR-21, miR-29a, miR-122, miR-155 and miR-181a and the phenotypic expression of NAFLD. A cross-sectional study was carried out on 108 NAFLD patients diagnosed by liver biopsy. FIB-4 and NAFLD fibrosis scores were calculated. The comparison between the distributions of microRNA values according to the presence or absence of histological fibrosis (F2-F4) was performed. A multivariate logistic regression analysis was performed to build a score for predicting fibrosis using FIB-4 and Ln (miR-181a) as independent variables. Only miR-181a showed a statistical difference between patients with significant liver fibrosis (>F2) and those without (F0-F1) (p = 0.017). FIB-4 revealed an AUC on the ROC curve of 0.667 to predict clinically significant fibrosis (F2-F4). When assessed using the score in association with Ln (miR-181a), there was an improvement in the ROC curve, with an AUC of 0.71. miR-181a can be used as a non-invasive method of predicting fibrosis in NAFLD, and an association with FIB-4 has the potential to increase the accuracy of each method alone.
- Synbiotic Supplementation Modulates Gut Microbiota, Regulates beta-Catenin Expression and Prevents Weight Gain in ob/ob Mice: Preliminary Findings(2022) DUARTE, Sebastiao Mauro B.; STEFANO, Jose Tadeu; FRANCO, Lucas A. M.; MARTINS, Roberta C.; MORAES, Bruna D. G. C.; BARBEIRO, Denise Frediani; OLIVEIRA, Nathalia; NERI, Junia Marielle Teixeira Rodrigues; COGLIATI, Bruno; VANNI, Denise Siqueira; SABINO, Ester C.; CARRILHO, Flair J.; OLIVEIRA, Claudia P.Background: Obesity is one of the main health problems in the world today, and dysbiosis seems to be one of the factors involved. The aim of this study was to examine the impact of synbiotic supplementation on obesity and the microbiota in ob/ob mice. Twenty animals were divided into four groups: obese treated (OT), obese control (OC), lean treated (LT) and lean control (LC). All animals received a standard diet for 8 weeks. The treated groups received a synbiotic (Simbioflora-Invictus Farmanutricao Ltd., Sao Paulo, Brazil) in water, while the nontreated groups received only water. After 8 weeks, all animals were sacrificed, and gut tissue and stool samples were collected for mRNA isolation and microbiota analysis, respectively. beta-Catenin, occludin, cadherin and zonulin in the gut tissue were analyzed via RT-qPCR. Microbiome DNA was extracted from stool samples and sequenced using an Ion PGM Torrent platform. Results: Synbiotic supplementation reduced body weight gain in the OT group compared with the OC group (p = 0.0398) and was associated with an increase in Enterobacteriaceae (p = 0.005) and a decrease in Cyanobacteria (p = 0.047), Clostridiaceae (p = 0.026), Turicibacterales (p = 0.005) and Coprococcus (p = 0.047). On the other hand, a significant reduction in Sutterella (p = 0.009) and Turicibacter (p = 0.005) bacteria was observed in the LT group compared to the LC group. Alpha and beta diversities were different among all treated groups. beta-Catenin gene expression was significantly decreased in the gut tissue of the OT group (p <= 0.0001) compared to the other groups. No changes were observed in occludin, cadherin or zonulin gene expression in the gut tissue. Conclusions: Synbiotic supplementation prevents excessive weight gain, modulates the gut microbiota, and reduces beta-catenin expression in ob/ob mice.
- MTP-493G/T gene polymorphism is associated with steatosis in hepatitis C-infected patients(2012) SIQUEIRA, E. R. F.; OLIVEIRA, C. P. M. S.; CORREA-GIANNELLA, M. L.; STEFANO, J. T.; CAVALEIRO, A. M.; FORTES, M. A. H. Z.; MUNIZ, M. T. C.; SILVA, F. S.; PEREIRA, L. M. M. B.; CARRILHO, F. J.The reduction of hepatic microsomal transfer protein (MTP) activity results in fatty liver, worsening hepatic steatosis and fibrosis in chronic hepatitis C (CHC). The G allele of the MTP gene promoter, -493G/T, has been associated with lower transcriptional activity than the T allele. We investigated this association with metabolic and histological variables in patients with CHC. A total of 174 untreated patients with CHC were genotyped for MTP -493G/T by direct sequencing using PCR. All patients were negative for markers of Wilson's disease, hemochromatosis and autoimmune diseases and had current and past daily alcohol intake lower than 100 g/week. The sample distribution was in Hardy-Weinberg equilibrium. Among subjects with genotype 1, 56.8% of the patients with fibrosis grade 3+4 presented at least one G allele versus 34.3% of the patients with fibrosis grade 1+2 (OR = 1.8; 95%CI = 1.3-2.3). Logistic regression analysis with steatosis as the dependent variable identified genotypes GG+GT as independent protective factors against steatosis (OR = 0.4, 95%CI = 0.2-0.8; P = 0.01). The results suggest that the presence of the G allele of MTP -493G/T associated with lower hepatic MTP expression protects against steatosis in our CHC patients.
- Fatty Pancreas: Disease or Finding?(2021) SILVA, Lucas de Lucena Simoes e; FERNANDES, Matheus Santos de Sousa; LIMA, Eline Autran de; STEFANO, Jose Tadeu; OLIVEIRA, Claudia P.; JUKEMURA, JoseDespite a growing number of investigative studies on pancreatic fat deposition, there remains no clear indication regarding the clinical relevance of fat infiltration in the pancreas, also called fatty pancreas (FP). An individual's body weight is correlated with their pancreatic weight. Moreover, lipid infiltration causes disorders that compromise not only morphology but also metabolic functions. Fat infiltration leads to insulin resistance, type II diabetes mellitus, and pancreatic cancer; however, knowledge about pancreatic fat content and aspects related to the clinical profile remains unclear in the literature. The present review describes the current knowledge of FP, including its pathophysiology and clinical implications, as well as lifestyle changes in FP.
- Non-pharmacological management options for MAFLD: a practical guide(2023) STEFANO, Jose Tadeu; DUARTE, Sebastiao Mauro Bezerra; ALTIKES, Renato Gama Ribeiro Leite; OLIVEIRA, Claudia P. P.Lifestyle changes should be the main basis for any treatment for metabolic dysfunction-associated fatty liver disease (MAFLD), aiming to increase energy expenditure, reduce energy intake and improve the quality of nutrients consumed. As it is a multifactorial disease, approaches such as physical exercise, a better dietary pattern, and possible pharmacological intervention are shown to be more efficient when used simultaneously to the detriment of their applications. The main treatment for MAFLD is a lifestyle change consisting of diet, activity, exercise, and weight loss. The variables for training prescription such as type of physical exercise (aerobic or strength training), the weekly frequency, and the intensity most indicated for the treatment of MAFLD remain uncertain, that is, the recommendations must be adapted to the clinical conditions comorbidities, and preferences of each subject in a way individual. This review addresses recent management options for MAFLD including diet, nutrients, gut microbiota, and physical exercise.
- S-nitroso-N-acetylcysteine attenuates liver fibrosis in experimental nonalcoholic steatohepatitis(2013) MAZO, Daniel F. C.; OLIVEIRA, Marcelo G. de; PEREIRA, Isabel V. A.; COGLIATI, Bruno; STEFANO, Jose T.; SOUZA, Gabriela F. P. de; RABELO, Fabiola; LIMA, Fabiana R.; ALVES, Venancio A. Ferreira; CARRILHO, Flair J.; OLIVEIRA, Claudia P. M. S. deS-Nitroso-N-acetylcysteine (SNAC) is a water soluble primary S-nitrosothiol capable of transferring and releasing nitric oxide and inducing several biochemical activities, including modulation of hepatic stellate cell activation. In this study, we evaluated the antifibrotic activity of SNAC in an animal model of nonalcoholic steatohepatitis (NASH) induced in Sprague-Dawley rats fed with a choline-deficient, high trans fat diet and exposed to diethylnitrosamine for 8 weeks. The rats were divided into three groups: SNAC, which received oral SNAC solution daily; NASH, which received the vehicle; and control, which received standard diet and vehicle. Genes related to fibrosis (matrix metalloproteinases [MMP]-13, -9, and -2), transforming growth factor beta-1 [TGF beta-1], collagen-1 alpha, and tissue inhibitors of metalloproteinase [TIMP-1 and -2] and oxidative stress (heat-shock proteins [HSP]-60 and -90) were evaluated. SNAC led to a 34.4% reduction in the collagen occupied area associated with upregulation of MMP-13 and -9 and downregulation of HSP-60, TIMP-2, TGF beta-1, and collagen-1 alpha. These results indicate that oral SNAC administration may represent a potential antifibrotic treatment for NASH.
article 64 Citação(ões) na Scopus Circulating levels of citrullinated and MMP-degraded vimentin (VICM) in liver fibrosis related pathology(2012) VASSILIADIS, Efstathios; OLIVEIRA, Claudia P.; ALVARES-DA-SILVA, Mario R.; ZHANG, Chen; CARRILHO, Flair J.; STEFANO, Jose T.; RABELO, Fabiola; PEREIRA, Leila; KAPPEL, Camila R.; HENRIKSEN, Kim; VEIDAL, Sanne Skovgard; VAINER, Ben; DUFFIN, Kevin L.; CHRISTIANSEN, Claus; LEEMING, Diana J.; KARSDAL, MortenAim: To investigate whether increased levels of vimentin citrullinated peptides identified by MS in articular cartilage can be measured in pathologies other than rheumatoid arthritis and be utilised for diagnostic purposes. Methods: A monoclonal antibody against the sequence RLRSSVPGV-citrulline (VICM) was developed and evaluated in a carbon tetrachloride (CCl4) (n=52 + 28 controls) rat model of liver fibrosis and two clinical cohorts of adult patients with hepatitis C (HCV) (n=92) and non-alcoholic fatty liver disease (NAFLD) (n=62), and compared to healthy controls. Results: In CCl4-treated rats, mean systemic VICM levels increased 31% at week 12 (176 ng/mL, P<0.001), 41.7% at weeks 16 (190 ng/mL, P<0.001), 49.2% at weeks 20 (200 ng/ml, P<0.001), compared to controls (134 ng/mL). VICM levels correlated with total hepatic collagen determined by Sirius red staining of rat livers (r=0.75, P<0.05). In the HCV cohort, when stratified according to the METAVIR F score, VICM levels were 63% higher in F0 (632 ng/mL +/- 75, p<0.05), 54% in F1 (597 ng/mL +/- 41.3, p<0.05) and 62% in F2 (628 ng/mL +/- 59, p<0.05) all compared to controls. In the NAFLD cohort, VICM levels were 20.6% higher in F0 (339 +/- 12 ng/mL, P<0.05), 23.8% in F1 (348 +/- 12 ng/mL, P<0.05) and 28.8% in F2 (362 +/- 25 P<0.05). Conclusion: We demonstrated increased serological levels of citrullinated and MMP degraded vimentin in an animal model of liver fibrosis and in early fibrosis associated with HCV and NAFLD patients. These data suggest that citrullinated and MMP degraded proteins are also present in liver fibrosis.- Effects of Aerobic Exercise Protocol on Genes Related to Insulin Resistance and Inflammation in the Pancreas of ob/ob Mice with NAFLD(2020) SILVA, Lucas Lucena Simoes e; FERNANDES, Matheus Santos de Sousa; KUBRUSLY, Marcia Saldanha; MULLER, Cynthia Rodrigues; AMERICO, Anna Laura Viacava; STEFANO, Jose Tadeu; EVANGELISTA, Fabiana Sant'Anna; OLIVEIRA, Claudia Pinto; JUKEMURA, JosePurpose: To evaluate the effect of 8 weeks of aerobic training on insulin resistance and inflammatory response in obese mice (ob/ob) with NAFLD. Materials and Methods: Male ob/ob mice were randomly divided into sedentary (n=7) and trained (n=7) groups. Aerobic training consisted of 5 weekly sessions, 60 min per session at 60% of the maximum speed of the running test. Hepatic and pancreatic samples were collected to evaluate histological features and gene expression associated with insulin resistance and inflammatory response after 8-week experiment protocol. RNA was performed by TRIzol (R). PCR experiments were performed using the Rotor-Gene RG-3000. Parametric data were assessed by t-test, one-way ANOVA and Bonferroni test for multiple comparisons. Non-parametric data were assessed by the Mann-Whitney tests with Dunn's post-test of multiple comparisons. Histological analysis was assessed by chi-square test with Fisher's exact test. Significant variables were considered when p<0.05. All the analyses were performed by GraphPad Prism V6.0 software (GraphPad Software Inc.). Results: Reductions in bodyweight (p = 0.008), weight evolution (p = 0.03), food intake (p <0.0001) and fat content were observed in trained group. Moreover, the trained group showed better results in peak velocity (p=0.03) physical effort tolerance (p=0.006) and distance (p=0.01). Gene expression showed differences in IL-10 (p=0.03) and GLUT-2 (p=0.03) in hepatic analysis, between groups. Pancreatic gene expression showed difference between groups in IRS-2 (p=0.004), GLUT-2 (p=0.03) and IL-10 (p=0.008) analysis. Also, the trained group showed lower values for interlobular fat and inflammatory infiltrate in histological analysis when compared to sedentary animals. Conclusion: An 8-week physical training protocol was able to attenuate bodyweight gain, food intake and generate positive effects on gene expression related to insulin resistance and inflammation in both liver and pancreas of ob/ob mice.
- N-ACETYLCYSTEINE AND/OR URSODEOXYCHOLIC ACID ASSOCIATED WITH METFORMIN IN NON-ALCOHOLIC STEATOHEPATITIS: AN OPEN-LABEL MULTICENTER RANDOMIZED CONTROLLED TRIAL(2019) OLIVEIRA, Claudia P; COTRIM, Helma P; STEFANO, Jose Tadeu; SIQUEIRA, Ana Cristina G; SALGADO, Ana Lucia Azevedo; PARISE, Edison RobertoABSTRACT BACKGROUND: Nowadays, pharmacological treatment of non-alcoholic fatty liver disease (NAFLD) is still limited and it is based on the treatment of conditions associated comorbities. Oxidative stress and insulin resistance are the mechanisms that seem to be mostly involved in its pathogenesis. OBJECTIVE: To evaluate the efficacy of N-acetylcysteine (NAC) in combination with metformin (MTF) and/or ursodeoxycholic acid (UDCA) for treatment of non-alcoholic steatohepatitis (NASH). METHODS: Open-label multicenter randomized trial was conducted for 48 weeks. It included patients with biopsy-proven NASH. The patients were randomized into three groups: NAC (1.2 g) + UDCA (15 mg/kg) + MTF (850-1500 mg/day) (n=26); UDCA (20 mg/kg) + MTF (850-1500 mg/day) (n=13); NAC (1.2g) + MTF (850-1500 mg/day) (n=14) for 48 weeks. Clinical, laboratory and the second liver biopsies were performed after 48 weeks. RESULTS: A total of 53 patients were evaluated; 17 (32.1%) were males; median age ±54 (IQR=15, 21-71) years. In the baseline, no difference was seen between groups according clinical and histological parameters. The groups differed only in cholesterol, LDL and triglycerides. No significant differences in biochemical and histologic parameters were found between these the three groups after 48 weeks of treatment. In the intragroup analysis (intention-to-treat) comparing histological and biochemical features, there were significant improvements in the steatosis degree (P=0.014), ballooning (0.027) and, consequently, in the NAFLD Activity Score (NAS) (P=0.005), and in the ALT levels at the end of the treatment only in the NAC + MTF group. No significant evidence of modification in the liver fibrosis could be observed in any of the groups. CONCLUSION: This multicenter study suggests that the association of NAC + MTF could reduce the liver disease activity in patients with NASH. These data stimulate further controlled studies with this therapy for these patients.
- Association of a variant in the regulatory region of NADPH oxidase 4 gene and metabolic syndrome in patients with chronic hepatitis C(2015) SIQUEIRA, Erika Rabelo Forte de; PEREIRA, Luciano Beltrao; STEFANO, Jose Tadeu; PATENTE, Thiago; CAVALEIRO, Ana Mercedes; VASCONCELOS, Luydson Richardson Silva; CARMO, Rodrigo Feliciano; PEREIRA, Leila Maria Moreira Beltrao; CARRILHO, Flair Jose; CORREA-GIANNELLA, Maria Lucia; OLIVEIRA, Claudia P.Background: Given the important contribution of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system to the generation of reactive oxygen species induced by hepatitis C virus (HCV), we investigated two single nucleotide polymorphisms (SNPs) in the putative regulatory region of the genes encoding NADPH oxidase 4 catalytic subunit (NOX4) and its regulatory subunit p22phox (CYBA) and their relation with metabolic and histological variables in patients with HCV. Methods: One hundred seventy eight naive HCV patients (49.3% male; 65% HCV genotype 1) with positive HCV RNA were genotyped using specific primers and fluorescent-labeled probes for SNPs rs3017887 in NOX4 and -675 T -> A in CYBA. Results: No association was found between the genotype frequencies of NOX4 and CYBA SNPs and inflammation scores or fibrosis stages in the overall population. The presence of the CA + AA genotypes of the NOX4 SNP was nominally associated with a lower alanine aminotransferase (ALT) concentration in the male population (CA + AA = 72.23 +/- 6.34 U/L versus CC = 100.22 +/- 9.85; mean +/- SEM; P = 0.05). The TT genotype of the CYBA SNP was also nominally associated with a lower ALT concentration in the male population (TT = 84.01 +/- 6.77 U/L versus TA + AA = 109.67 +/- 18.37 U/L; mean +/- SEM; P = 0.047). The minor A-allele of the NOX4 SNP was inversely associated with the frequency of metabolic syndrome (MS) in the male population (odds ratio (OR): 0.15; 95% confidence interval (CI): 0.03 to 0.79; P = 0.025). Conclusions: The results suggest that the evaluated NOX4 and CYBA SNPs are not direct genetic determinants of fibrosis in HCV patients, but nevertheless NOX4 rs3017887 SNP could indirectly influence fibrosis susceptibility due to its inverse association with MS in male patients.
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